Abstract 4142: Modulation of kinase signaling by APLP2 in pancreatic cancer cells

Abstract Pancreatic cancer is a highly aggressive malignancy with few effective treatment options, highlighting the importance of understanding its underlying molecular mechanisms. The overexpression of amyloid precursor-like protein 2 (APLP2) in pancreatic cancer suggests that it may promote cancer progression. However, mechanisms by which APLP2 may influence critical signaling pathways in pancreatic cancer remain undefined. To address this, a membrane-based sandwich immunoassay was used to determine the relative phosphorylation levels of 37 kinase sites in S2-013 pancreatic cancer cell lysates following siRNA-mediated APLP2 knockdown. The results demonstrated that the downregulation of APLP2 led to significant changes in the phosphorylation of several key kinases, including a pronounced increase in the phosphorylation of the proline-rich Akt substrate of 40 kDa (PRAS40), which is involved in mTORC1 function, and decreases in the phosphorylation of CREB, ERK1/2, and JNK 1/2/3. Qiagen Ingenuity Pathway Analysis (IPA) identified that the pathways most affected by APLP2 knockdown involved MAPK targets and nuclear events mediated by MAP kinases. Together, these findings suggest that APLP2 may regulate key signaling pathways driving pancreatic cancer progression and provide insights into the molecular mechanisms by which APLP2 contributes to pancreatic cancer’s aggressive nature. Our future studies will utilize chemical inhibitors, knockout experiments, and western blot analysis to validate and extend these new findings. Citation Format: Kenadie Doty, Kaitlin J. Smith, Gabrielle L. Brumfield, Joyce C. Solheim. Modulation of kinase signaling by APLP2 in pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4142.